Obesity-related increases in adipose tissue macrophages leading to inflammation and insulin resistance.

Research
Description

Research description:
The growing worldwide obesity epidemic is frequently linked to hyperlipidemia, inflammation, and insulin resistance leading to increased risk of diabetes and cardiovascular disease. The long-term goal of my laboratory is to determine mechanisms by which obesity increases risk for and pathophysiological consequences of these devastating diseases. Macrophages are part of the innate immune system that infiltrate white adipose tissue in obese rodents and humans, and produce most of the inflammatory cytokines and chemokines secreted from AT. In addition, their presence has been shown to be temporally associated with the development of insulin resistance. My current research focus is to determine mechanisms by which macrophages are attracted to adipose tissue and what happens to them once they arrive. Some of the current projects in my laboratory are:

Macrophage Cell Death: The macrophages in adipose tissue are exposed to high levels of fatty acids that are released from the adipocytes either due to uncontrolled lipolysis or adipocyte cell death. We have evidence in vitro, that exposure of macrophages to saturated fatty acids induced inflammation, ER stress and apoptosis. However, it has not been determined whether ATMs undergo apoptosis. In addition, apoptotic cells are normally phagocytosed by other macrophages in a process called a??efferocytosisa??. It is also now known whether efferocytosis can occur in AT in vivo. We are interested in whether efferocytosis occurs in AT and whether this can contribute to resolution of the inflammation.

Turnover of Adipose Tissue Macrophages: We have growing evidence that even in lean adipose tissue the macrophages undergo apoptotic cell death. We would like to understand how the natural turnover of macrophages contributes to the overall numbers of cells in lean and obese adipose tissue. We hypothesize that this turnover may be impaired in obesity and contribute to the accumulation of macrophages in obese adipose tissue.

Macrophage Emigration: In addition to studying mechanisms by which macrophages enter adipose tissue, we are also performing experiments to determine how their numbers decline during weight loss. This may be via increased turnover or apoptosis as described above. However, an alternative would be that they could emigrate out of adipose tissue. We have a mouse model where leukocyte emigration from tissue to nearby lymph nodes is impaired. We would like to study adipose tissue macrophage emigration in this model.